DESCRIPTION: (APPLICANT'S ABSTRACT) The neurotransmitter, dopamine (DA), plays a central role in motivation and reward. In addition, the reinforcing properties of many drugs of abuse are thought to be critically dependent on mesolimbic DA function. This is particularly true for stimulant drugs such as cocaine and amphetamine. Analogously to these stimulants, opiate drugs such as morphine are considered highly rewarding and reinforcing; however, the involvement of DA in opiate reward is less clear. The proposed studies address this issue by examining the oral self-administration of cocaine and of morphine by DA-deficient and wild type control mice. Sucrose is used to increase the palatability of the drug solution, and a sucrose-fading technique is used to gradually reduce the sucrose component. Once the drug is readily consumed in the absence of sucrose, the animals will receive a preference test, allowing them to choose between water and the drug solution. If DA is critical for cocaine to be reinforcing, then DA-deficient mice should not be expected to prefer the cocaine solution over water, whereas wild-type mice should. Conversely, if morphine intake does not depend on DA, but instead, acts primarily through an independent opiate system, then mice lacking in DA should show a similar preference to that of wild-type mice for the morphine solution. Research with DA-deficient mice provides a unique opportunity to gain new insight into the neuropharmacological basis of drug reward.